rs11568828

Variant names:

• chr17-63918913-T-C
• rs11568828
• ENST00000647774.1:c.287-407A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-63918913-T-C
• chr17-63918913-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000647774.1(ENSG00000285947):​c.287-407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,529,780 control chromosomes in the GnomAD database, including 9,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (732 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8428 hom.)
• Consequence: ENSG00000285947 ENST00000647774.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.25
• Publications: 12 publications found

Genes affected

ENSG00000285947 (HGNC:):

GH1 (HGNC:4261): (growth hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]

GH1 Gene-Disease associations (from GenCC):

• isolated growth hormone deficiency type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• isolated growth hormone deficiency type II

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• isolated growth hormone deficiency type IB

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short stature due to growth hormone qualitative anomaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-63918913-T-C is Benign according to our data. Variant chr17-63918913-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647774.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	NM_000515.5	MANE Select	c.-137A>G		upstream_gene	N/A	NP_000506.2
	GH1	NM_022559.4		c.-137A>G		upstream_gene	N/A	NP_072053.1
	GH1	NM_022560.4		c.-137A>G		upstream_gene	N/A	NP_072054.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285947	ENST00000647774.1		c.287-407A>G		intron	N/A	ENSP00000497443.1
	GH1	ENST00000323322.10	TSL:1 MANE Select	c.-137A>G		upstream_gene	N/A	ENSP00000312673.5
	GH1	ENST00000458650.6	TSL:1	c.-137A>G		upstream_gene	N/A	ENSP00000408486.2

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13759 AN: 152034 Hom.: 733 Cov.: 33

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.106 AC: 146018 AN: 1377628 Hom.: 8428 AF XY: 0.105 AC XY: 71819 AN XY: 685586

African (AFR) AF: 0.0470 AC: 1460 AN: 31054

American (AMR) AF: 0.0733 AC: 2868 AN: 39148

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3603 AN: 24900

East Asian (EAS) AF: 0.0366 AC: 1396 AN: 38092

South Asian (SAS) AF: 0.0523 AC: 4284 AN: 81896

European-Finnish (FIN) AF: 0.107 AC: 5573 AN: 51912

Middle Eastern (MID) AF: 0.148 AC: 828 AN: 5608

European-Non Finnish (NFE) AF: 0.114 AC: 119936 AN: 1047606

Other (OTH) AF: 0.106 AC: 6070 AN: 57412

GnomAD4 genome AF: 0.0904 AC: 13762 AN: 152152 Hom.: 732 Cov.: 33 AF XY: 0.0886 AC XY: 6588 AN XY: 74394

African (AFR) AF: 0.0469 AC: 1944 AN: 41454

American (AMR) AF: 0.0830 AC: 1269 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3472

East Asian (EAS) AF: 0.0371 AC: 192 AN: 5174

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10616

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7938 AN: 68010

Other (OTH) AF: 0.115 AC: 242 AN: 2108

Alfa AF: 0.0938 Hom.: 84

Bravo AF: 0.0887

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.74
PhyloP100		3.2
PromoterAI		-0.0040	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11568828; hg19: chr17-61996273;